[New tools for medication review: DRP in patients treatment with proton pump inhibitors]. / Nuevas herramientas para la revisión de la medicación: PRM en pacientes en tratamiento con inhibidores de la bomba de protones.

OBJECTIVE: To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. DESIGN: Descriptive and retrospective observational study. MATERIAL AND METHODS: The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). RESULTS: The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. CONCLUSIONS: The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments.

[Diagnostic performance of biliopancreatic endosonography in patients with intermediate risk of choledocholithiasis]. / Rendimiento diagnóstico de la endosonografía biliopancreática en pacientes con riesgo intermedio de coledocolitiasis.

OBJECTIVE: Determine the sensitivity and specificity of the ESBP for diagnosis in patients with intermediate risk of choledocholithiasis, referred to the specialized surgical Gastroenterology center of Unión de Cirujanos SAS - Oncologists of the West Zentria group - Manizales - Colombia between March 01, 2020 to January 31, 2022. MATERIALS AND METHODS: Retrospective cross-sectional study in patients with intermediate risk for choledocholithiasis. The diagnostic performance of ESBP was calculated and confirmed with ERCP. Negative ESBPs were followed up by telephone. RESULTS: 752 cases with ESBP were analyzed, of which 43.2% (n=325) were positive and 56.8% (n=427) were negative. ERCP was performed in positive cases who accepted the procedure (n=317); 73.5% (n:233) were positive for choledocholithiasis, 25.8% (n=82) tumors and 0.6% (n=2) biliary roundworms. Patients with positive ESBP underwent ERCP. S= 98.3% (95% CI: 95.7-99.5) was obtained; E= 88.1% (95% CI: 79.2-94.1); PPV = 95.8% (95% CI: 92.4-98.0); NPV = 94.9% (95% CI: 87.4-98.7). The AUC of ESBP was 0.9319 (95% CI 0.8961-0.967). CONCLUSION: In patients with intermediate risk for choledocholithiasis, ESBP is a useful diagnostic option in the study of pancreatic pathologies, extrahepatic biliary tree, and the identification of biliary microlithiasis; Therefore, it also allows us to complement it with a therapeutic intervention such as ERCP in a single time.

TMPRSS11a is a novel age-altered, tissue specific regulator of migration and wound healing.

Aging is a gradual biological process characterized by a decrease in cellular and organism functions. Aging-related processes involve changes in the expression and activity of several proteins. Here, we identified the transmembrane protease serine 11a (TMPRSS11a) as a new age-specific protein that plays an important role in skin wound healing. TMPRSS11a levels increased with age in rodent and human skin and gingival samples. Strikingly, overexpression of TMPRSS11a decreased cell migration and spreading, and inducing cellular senescence. Mass spectrometry, bioinformatics, and functional analyses revealed that TMPRSS11a interacts with integrin ß1 through an RGD sequence contained within the C-terminal domain and that this motif was relevant for cell migration. Moreover, TMPRSS11a was associated with cellular senescence, as shown by overexpression and downregulation experiments. In agreement with tissue-specific expression of TMPRSS11a, shRNA-mediated downregulation of this protein improved wound healing in the skin, but not in the skeletal muscle of old mice, where TMPRSS11a is undetectable. Collectively, these findings indicate that TMPRSS11a is a tissue-specific factor relevant for wound healing, which becomes elevated with aging, promoting cellular senescence and inhibiting cell migration and skin repair.

Effect of High-velocity Resistance Exercise on 24-h Blood Pressure in Hypertensive Older Women.

This study investigated the acute post-exercise effect of high-velocity resistance exercise on ambulatory blood pressure in hypertensive older women. Fourteen volunteers (67.9±5.1 years) performed a high-velocity resistance exercise session (8 exercises using Thera-Band, 3 sets of 6 repetitions as fast as possible in the concentric phase with moderate intensity) and a control session, separated by a 7-10-day period. Ambulatory blood pressure was monitored following 12-h post-sessions and compared between conditions at 1 to 4-h, 5 to 8-h, and 9 to 12-h. Average 24-h ambulatory blood pressure, awake, asleep periods, and blood pressure load were also analyzed. There was a condition by time interaction for systolic ambulatory blood pressure over 12-h post-sessions (P=0.043). It was observed a lower systolic ambulatory blood pressure in the first 4-h period following the high-velocity resistance exercise session compared to the control session (-6.7 mmHg, 95% CI - 11.6 to -1.8 mmHg; P=0.011). No changes were observed for diastolic ambulatory blood pressure over 12-h post-sessions as well as for the other variables analyzed (P>0.05). In summary, a single high-velocity resistance exercise session elicits a post-exercise antihypertensive effect and may be considered as a strategy to acutely improve blood pressure control in hypertensive older women.

Effects of Isometric Biceps Exercise on Blood Pressure in Adults with Hypertension.

We investigated the acute effects of isometric biceps exercise on resting and ambulatory blood pressure in hypertensive adults. A total of 12 medicated hypertensive adults (aged 47±7 years; body mass index 27.2±2.7 kg/m2; resting blood pressure 123±12/74±6 mmHg) performed an isometric biceps exercise session (bilateral biceps exercise; 4×1 min at 30% of 1-RM, 2 min recovery) and a control session (without exercise) in a randomized order separated by a 7 to 10-day period. Resting blood pressure, heart rate, and heart rate variability indexes (SDNN, RMSSD, LF, HF, and LF/HF) were measured pre- and up to 30 min post-sessions. Next, ambulatory blood pressure was monitored during 22-hour post-sessions (awake and asleep periods). No significant changes were observed for resting blood pressure, heart rate, or heart rate variability indexes up to 30 min post-sessions (p>0.05). Furthermore, no significant differences were observed in average ambulatory blood pressure values in 22-hour (126±11/71±6 mmHg vs. 126±15/71±9 mmHg), awake (127±10/74±6 mmHg vs. 130±14/75±10 mmHg), and asleep (123±15/68±6 mmHg vs. 120±17/66±9 mmHg) periods between the control and isometric sessions, respectively (p>0.05). In conclusion, an isometric biceps exercise session does not elicit an acute antihypertensive effect in adults with hypertension, which suggests that its prescription to improve the acute BP control is limited.

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells.

OBJECTIVE: Liver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation. DESIGN: The effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms. RESULTS: RPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism. CONCLUSION: RPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV's actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.

Physiological and Psychological Responses during Low-Volume High-Intensity Interval Training Sessions with Different Work-Recovery Durations.

We compared physiological and psychological responses between low-volume high-intensity interval training (LV-HIIT) sessions with different work-recovery durations. Ten adult males performed two LV-HIIT sessions in a randomized, counter-balanced order. Specifically, 60/60 s LV-HIIT and 30/30 s LV-HIIT. Oxygen uptake (VO2), carbon dioxide output (VCO2), ventilation (VE), respiratory exchange ratio (RER), perceived exertion (RPE), and affect were assessed. During intervals, the VO2 (3.25 ± 0.57 vs. 2.83 ± 0.50 L/min), VCO2 (3.15 ± 0.61 vs. 2.93 ± 0.58 L/min), VE (108.59 ± 27.39 vs. 94.28 ± 24.98 L/min), and RPE (15.9 ± 1.5 vs. 13.9 ± 1.5) were higher (ps ≤ 0.01), while RER (0.98 ± 0.05 vs. 1.03 ± 0.03) and affect (-0.8 ± 1.4 vs. 1.1 ± 2.0) were lower (ps ≤ 0.007) in the 60/60 s LV-HIIT. During recovery periods, VO2 (1.85 ± 0.27 vs. 2.38 ± 0.46 L/min), VCO2 (2.15 ± 0.35 vs. 2.44 ± 0.45 L/min), and affect (0.6 ± 1.7 vs. 1.7 ± 1.8) were lower (ps ≤ 0.02), while RER (1.20 ± 0.05 vs. 1.03 ± 0.05; p < 0.001) was higher in the 60/60 s LV-HIIT. Shorter LV-HIIT (30 s) elicits lower physiological response and attenuated negative affect than longer LV-HIIT (60 s).

Thermal liquid biopsy for monitoring melanoma patients under surveillance during treatment: A pilot study.

BACKGROUND: Differential Scanning Calorimetry (DSC) is a technique traditionally used to study thermally induced macromolecular transitions, and it has recently been proposed as a novel approach for diagnosis and monitoring of several diseases. We report a pilot study applying Thermal Liquid Biopsy (TLB, DSC thermograms of plasma samples) as a new clinical approach for diagnostic assessment of melanoma patients. METHODS: Multiparametric analysis of DSC thermograms of patient plasma samples collected during treatment and surveillance (63 samples from 10 patients) were compared with clinical and diagnostic imaging assessment to determine the utility of thermograms for diagnostic assessment in melanoma. Nine of the ten patients were stage 2 or 3 melanoma subjects receiving adjuvant therapy after surgical resection of their melanomas. The other patient had unresectable stage 4 melanoma and was treated with immunotherapy. Two reference groups were used: (A) 36 healthy subjects and (B) 13 samples from 8 melanoma patients who had completed successful surgical management of their disease and were determined by continued clinical assessment to have no evidence of disease. RESULTS: Plasma thermogram analysis applied to melanoma patients generally agrees with clinical evaluation determined by physical assessment or diagnostic imaging (~80% agreement). No false negatives were obtained from DSC thermograms. Importantly, this methodology was able to detect changes in disease status before it was identified clinically. CONCLUSIONS: Thermal Liquid Biopsy could be used in combination with current clinical assessment for the earlier detection of melanoma recurrence and metastasis. GENERAL SIGNIFICANCE: TLB offers advantages over current diagnostic techniques (PET/CT imaging), limited in frequency by radiation burden and expense, in providing a minimally-invasive, low-risk, low-cost clinical test for more frequent personalized patient monitoring to assess recurrence and facilitate clinical decision-making.

Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells.

Shikonin is the main active principle in the root of Lithospermum erythrorhizon, widely used in traditional Chinese medicine for its anti-inflammatory and wound healing properties. Recent research highlights shikonin's antitumor properties and capacity to prevent acute ulcerative colitis. The aim of the present study was to evaluate the ability of shikonin to prevent, in vivo, the early phases of colorectal cancer development, with special focus on its cytotoxic mechanism in vitro. We employed the azoxymethane/dextran sulfate sodium model of colitis in Balb/C mice. Body weight and drinking were monitored throughout the experiment, and length of colon and lesions of the colon were recorded on termination of the experiment in all of the experimental groups. Colons underwent histological evaluation and biochemical analyses [myeloperoxidase activity assay, measurement of interleukin-6, evaluation of proinflammatory enzymes (cyclooxygenase-2 and inducible nitric oxide synthase), and nuclear factor-κB activation by Western blot]. Caco-2 cells were used to evaluate, in vitro, the effect of shikonin on proliferation, cytotoxicity, cell cycle, and apoptosis. Our results reveal that shikonin significantly protected the intestinal tissue of our animals by preventing the shortening of the colorectum and ulcer formation in a dose-dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the production of interleukin-6 and activation of nuclear factor-κB. It induced Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive agent in the azoxymethane/dextran sulfate sodium model through inhibition of the proinflammatory milieu generated during the disease, an important risk factor in cancer development.

The purine analogues abacavir and didanosine increase acetaminophen-induced hepatotoxicity by enhancing mitochondrial dysfunction.

BACKGROUND: NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. METHODS: We evaluated the acute effects of clinically relevant concentrations of the most widely used NRTIs, alone or combined with acetaminophen, on mitochondrial function and cellular viability. RESULTS: The purine analogues abacavir and didanosine produced an immediate and concentration-dependent inhibition of oxygen consumption and complex I and III activity. This inhibition was accompanied by an undermining of mitochondrial function, with increased production of reactive oxygen species and reduction of mitochondrial membrane potential and intracellular ATP levels. However, this interference did not compromise cell survival. Co-administration with concentrations of acetaminophen below those considered hepatotoxic exacerbated the deleterious effects of both compounds on mitochondrial function and compromised cellular viability, showing a clear correlation with diminished glutathione levels. CONCLUSIONS: The simultaneous presence of purine analogues and low concentrations of acetaminophen significantly potentiates mitochondrial dysfunction, increasing the risk of liver injury. This new mechanism is relevant given the liver's susceptibility to mitochondrial dysfunction-related toxicity and the tendency of the HIV infection to increase oxidative stress.

Rosmarinic acid improves function and in vitro fertilising ability of boar sperm after cryopreservation.

During cryopreservation, oxidative stress exerts physical and chemical changes on sperm functionality. In the present study we investigated the antioxidant effect of rosmarinic acid (RA) on quality and fertilising ability of frozen-thawed boar spermatozoa. Ejaculates collected from mature boar were cryopreserved in lactose-egg yolk buffer supplemented with different concentrations of RA (0 µM, 26.25 µM, 52.5 µM and 105 µM). Motion parameters, acrosome and plasma membrane integrity, lipoperoxidation levels, DNA oxidative damage (8-hydroxy-2-deoxyguanosine base lesion) and in vitro fertilisation ability were evaluated. Total and progressive motility were significantly higher in experimental extenders with RA than in the control (P<0.05) at 0 and 120 min post-thawing. The plasma and acrosomal membrane integrity were improved by supplementation with 105 µMRA (P<0.05). Negative correlation between RA and malondialdehyde (MDA) concentration were determined (P<0.05). After thawing, the percentage of spermatozoa with oxidised DNA did not differ between extenders, however, at 120 and 240 min post-thawing, the samples supplemented with 105 µMRA showed the lowest DNA oxidation rate (P<0.05). The penetration rate was significantly higher on spermatozoa cryopreserved with 105 µMRA (P<0.05). The results suggest that RA provides a protection for boar spermatozoa against oxidative stress during cryopreservation by their antioxidant properties.

Automatic processes moderate the association between reflective processes and movement behavior: A cross-sectional study.

Dual-process theories postulate that both reflective and automatic processes regulate health behavior. Further research is required to test the basic postulates of dual-process theories. We investigated the direct associations and moderating effect between automatic processes and multiple indicators of reflective processes on various levels of physical activity and sedentary behavior assessed using accelerometry in adults who were not participating in regular physical exercise programs. This cross-sectional study included 257 adults. Each participant completed a computerized test for automatic associations, a set of questions assessing reflective processes, a seven-day assessment using accelerometers to determine their levels of physical activity and sedentary behavior. The results showed a direct relationship between perceived benefits (B = 15.90, p = 0.043), perceived cons (B = -12.81, p = 0.034), decisional intention (B = -0.07, p = 0.049) with light physical activity, and self-efficacy with daily steps (B = 485.71, p = 0.008). There was a positive association between intention strength and daily steps when implicit associations favored physical activity (b = 623.36, LLCI = 79.09, ULCI = 1167.62, p = 0.025); a negative association between self-efficacy and sedentary behavior when implicit associations favored sedentary behavior (b = -25.73, LLCI = -49.77, ULCI = -1.70, p = 0.035); and a positive association between intention strength and sedentary behavior when implicit associations favored physical activity (b = 34.18, LLCI = 8.81, ULCI = 59.56, p = 0.008). These findings underscore the importance of considering the interplay between reflective and automatic processes in shaping movement behavior.

Associations of upper- and lower-limb muscle strength, mass, and quality with health-related quality of life in community-dwelling older adults.

AIM: This study aimed to investigate the associations between upper- and lower-limb muscle strength, mass, and quality and health-related quality of life (HRQoL) among community-dwelling older adults. METHODS: A cross-sectional study was conducted with 428 Brazilian community-dwelling older adults aged 60 to 80 years. Upper- and lower-limb muscle strength were evaluated through the handgrip strength (HGS) test and the 30-s chair stand test, respectively. Muscle mass was assessed by dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA). Muscle quality was evaluated using the muscle quality index (MQI). HRQoL was assessed using the World Health Organization Quality of Life Brief Version questionnaire. RESULTS: Lower-limb, but not upper-limb, muscle strength and quality were independently associated with HRQoL, particularly within the domains of physical capacity, environment, and overall HRQoL for both males and females (P < 0.05). DXA- and BIA-derived analyses provided similar results in relation to muscle mass and muscle quality. CONCLUSIONS: Lower-limb, but not upper-limb, muscle strength and quality were independently associated with HRQoL among community-dwelling older adults. Moreover, the results obtained from both BIA and DXA were similar, highlighting that BIA can serve as a viable surrogate method for estimating body composition in resource-limited clinical settings. Geriatr Gerontol Int 2024; 24: 683-692.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes.

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Metabolomic analysis reveals stress tolerance mechanisms in common bean (Phaseolus vulgaris L.) related to treatment with a biostimulant obtained from Corynebacterium glutamicum.

Microbial biostimulants have emerged as a sustainable alternative to increase the productivity and quality of important crops. Despite this, the effects of the treatment on plant metabolism are poorly understood. Thus, this study investigated the metabolic response of common bean (Phaseolus vulgaris) related to the treatment with a biostimulant obtained from the extract of Corynebacterium glutamicum that showed positive effects on the development, growth, and yield of crops previously. By untargeted metabolomic analysis using UHPLC-MS/MS, plants and seeds were subjected to treatment with the biostimulant. Under ideal growth conditions, the plants treated exhibited higher concentration levels of glutamic acid, nicotiflorin and glycosylated lipids derived from linolenic acid. The foliar application of the biostimulant under water stress conditions increased the chlorophyll content by 17% and induced the accumulation of flavonols, mainly quercetin derivatives. Also, germination seed assays exhibited longer radicle lengths for seeds treated compared to the untreated control even in the absence of light (13-18% increase, p-value <0.05). Metabolomic analysis of the seeds indicated changes in concentration levels of amino acids (tryptophan, phenylalanine, tyrosine, glutamine, and arginine) and their derivatives. The results point out the enhancement of abiotic stress tolerance and the metabolic processes triggered in this crop associated with the treatment with the biostimulant, giving the first insights into stress tolerance mechanisms in P. vulgaris.

Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia.

Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. Methods: A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020-2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Results: Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. Conclusions: We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Clinicopathological predictors of survival in resected primary lung adenocarcinoma.

AIMS: Primary lung adenocarcinoma consists of a spectrum of clinical and pathological subtypes that may impact on overall survival (OS). Our study aims to evaluate the impact of adenocarcinoma subtype and intra-alveolar spread on survival after anatomical lung resection and identify different prognostic factors based on stage and histological subtype. METHODS: Newly diagnosed patients undergoing anatomical lung resections without induction therapy, for pT1-3, N0-2 lung adenocarcinoma from April 2011 to March 2013, were included. The effect of clinical-pathological factors on survival was retrospectively assessed. RESULTS: Two hundred and sixty-two patients were enrolled. The 1-year, 3-year and 5-year OS were 88.8%, 64.3% and 51.1%, respectively. Univariate analysis showed lymphovascular, parietal pleural and chest wall invasion to confer a worse 1-year and 5-year prognosis (all p<0.0001). Solid predominant adenocarcinomas exhibited a significantly worse OS (p=0.014). Multivariate analysis did not identify solid subtype as an independent prognostic factor; however, identified stage >IIa, lymphovascular invasion (p=0.002) and intra-alveolar spread (p=0.009) as significant independent predictors of worse OS. Co-presence of intra-alveolar spread and solid predominance significantly reduced OS. Disease-free survival (DFS) was reduced with parietal pleural (p=0.0007) and chest wall invasion (p<0.0001), however, adenocarcinoma subtype had no significant impact on DFS. CONCLUSIONS: Our study demonstrates that solid predominant adenocarcinoma, intra-alveolar spread and lymphovascular invasion confer a worse prognosis and should be used as a prognostic tool to determine appropriate adjuvant treatment.

Consensus on prevention and treatment of cancer-associated thrombosis (CAT) in controversial clinical situations with low levels of evidence.

BACKGROUND: Cancer patients suffer high risk of venous thromboembolism (VTE). Cancer-associated VTE (CAT) causes hospitalization, morbidity, delayed cancer treatment, and mortality; therefore, exceptional CAT prevention and management are imperative. METHODS: This review offers practical recommendations and treatment algorithms for eight complex, clinically relevant situations posing great uncertainty regarding management and requiring an urgent decision: VTE prophylaxis in ambulatory cancer patients with pancreatic pancreas (1) or lung cancer with molecular alterations (2); optimal management of VTE during antineoplastic treatment with antiangiogenics (3) or chemotherapy (4); protracted VTE treatment, determinants; (5) drugs used (6), and optimal VTE management in situations of high bleeding risk (7) or recurrent VTE (8). RESULTS: With the evidence available, primary thromboprophylaxis in patients with lung cancer harbouring ALK/ROS1 translocations or pancreatic cancer receiving ambulatory chemotherapy must be appraised. If antiangiogenic therapy can yield a clear benefit and the patient recovers from a grade 3 thrombotic event, it can be cautiously re-introduced in selected cases, provided that the person agrees to assume the risk after being duly informed. Anticoagulation maintenance beyond 6 months is recommended in individuals with metastatic tumours, on active treatment, or at high risk for recurrent VTE without bleeding risk. In such cases, LMWH and DOACs are safe, being mindful that the latter could entail a higher risk of bleeding; consequently, they should be used judiciously in more haemorrhagic tumours, such as gastrointestinal cancers. In cases of recurrent VTE, the presence of active cancer, infra-therapeutic dose, and anticoagulant treatment failure must be ruled out. In individuals with platelet counts of 25,000-50,000 and VTE liable to recur who need anticoagulation, full-dose LMWH and transfusion support can be contemplated to reach values of > 50,000. In CAT unlikely to recur, decreasing the LMWH dose by 25-50% is recommended. Renal impairment associated with thrombosis must be treated with LMWHs; there is no need to adjust the dose in patients with CrCl > 30; with CrCl = 15-30, dose adjustment is advised, and suspended when CrCl is < 15. CONCLUSION: We provide useful advice for complex, clinically relevant situations that clinicians treating CAT must face devoid of any unequivocal, strong, evidence-based recommendations.